Annual report: EB000087-03 This is a report of the Molecular Tracer and Imaging Core Facility of the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The major theme of our work is to utilize radionuclides for diagnostic and therapeutic purposes. We also have capabilities in chemical synthesis and evaluation of optical imaging probes. The laboratory is well equipped with analytical chemistry equipment to allow identity and purity analyses to be conducted on entities ranging from small molecules to large proteins. This equipment includes high resolution liquid chromatography-mass spectrometry, gas chromatography mass spectrometry, and NMR spectroscopy. We also house PET/CT and optical imaging devices in our laboratory. The majority of our work has been conducted as collaboration with the group of Dr. Xiaoyuan Chen, senior investigator, Laboratory of Molecular Imaging and Nanomedicine (LOMIN), NIBIB. We have projects with other investigators from outside of NIBIB, but these represented a small portion of our time. The projects with LOMIN are highly collaborative; we provide chemistry and radiochemistry services for the projects; the radionuclide image acquisition and image processing are joint efforts with the CORE personnel serving as trainer and/or mentor for LOMIN students and post-doctoral scientists, in some cases. Data interpretation and manuscript preparation are joint efforts among LOMIN and CORE members. 1) LOMIN collaborative projects. a. An Evans blue analog was previously developed in LOMIN and has demonstrated improved image contrast for diagnostic purposes and enhanced radiotherapeutic efficacy due to its albumin binding properties. During this reporting period, the Evans blue analog has been attached to other known peptides and small molecules in order to evaluate the scope of the beneficial effects. b. The previous application of the Evans blue moiety to the somatostatin binding peptide DOTATATE and one of the several PSMA binding ligands has resulted in markedly enhanced tumor uptake in xenograft models. The therapeutic efficacy using Lu-177 or Y-90 has been excellent using low doses (100 -200 uCi), although kidney uptake is a confound. LOMIN is actively pursuing outside collaboration to conduct studies in human subjects with this generation of compounds. c. In this reporting period, our activities have supported efforts to validate radiolabeling kits that will be used in subsequent therapeutic studies. d. Another goal of our LOMIN collaborator is the development of novel nanomaterials. This continues to be a significant portion of our radiochemical effort. We contributed to this project by assisting in the development of radiolabeling methods for the various particles under investigation in LOMIN. PET imaging of the radiolabeled nanomaterials provides information on the pharmacokinetics and biodistribution of these novel nanoparticles. LOMIN personnel can use this information to modify the nanoparticle design to achieve more desirable targeting or improved pharmacokinetics. 2) NIDDK collaborative projects a. From 1b) the EB-TATE conjugate is of interest to this collaborator for therapy of tumor models containing somatostatin receptors. We have been using imaging methods to evaluate their tumor models. The first therapeutic studies were conducted this year; and more studies are planned with new tumor models. 3) We have a mass spectrometry laboratory with two high resolution HPLC-MS systems. One of the instruments (Waters QTOF) is almost exclusively used to conduct characterization of chemicals synthesized in LOMIN or by Core Facility personnel. The second (Thermo Q-exactive), which promises higher mass resolution, is being evaluated to conduct studies of binding interactions between albumin and chemically synthesized binding molecules. This instrument also has capability in proteomics and may prove useful to other collaborators. 4) NIDCR project. An investigator in NIDCR wishes to apply PET imaging for one of their projects. We have worked with them to amend their protocol for use of our facility and radioactive materials. This project is now ongoing with regularly scheduled PET imaging studies using F-18 fluoride as the molecular tracer.